Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl-lactones, (-)-cryptomeridiol, liriodenine, 3-methyl-1H-benz[f]indole-4,9-dione, (-)-stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using (3) H-PAF as a ligand. Among the compounds tested, (-)-cryptomeridiol, (+)-goniothalamin and (+)-isoaltholactone exhibited a significant and concentration-dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)(50) values of 17.5, 19.7 and 46.5 µm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors.
Alzheimer's disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells. The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice. Ascorbic acid (100 mg/kg, p.o.) was used as a standard drug. The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease.
In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6-shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29 cells were confirmed using dual staining fluorescence microscopy and enzyme-linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic-related markers were determined in HT-29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3, survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids.
Vernonia amygdalina (VA) is a medicinal tropical herb for diabetes and malaria and believed to be beneficial for joint pains. The antiosteorthritis effects of VA leaf in cartilage explant assays and on postmenopausal osteoarthritis (OA) rat model were investigated. The VA reduced the proteoglycan and nitric oxide release from the cartilage explants with interleukin 1β (IL-1β) stimulation. For the preclinical investigation, ovariectomized (OVX) female rats were grouped (n = 8) into nontreated OA, OA + diclofenac (5 mg/kg), OA + VA extract (150 and 300 mg/kg), and healthy sham control. Monosodium iodoacetate was injected into the knee joints to accelerate OA development. After 8 weeks, the macroscopic, microscopic, and histological images showed that the OA rats treated with VA 300 mg/kg and diclofenac had significantly reduced cartilage erosions and osteophytes unlike the control OA rats. The extract significantly down-regulated the inflammatory prostaglandin E2, nuclear factor κβ, IL-1β, ADAMTS-5, collagen type 10α1, and caspase3 in the OVX-OA rats. It up-regulated the anti-inflammatory IL-10 and collagen type 2α1 mRNA expressions, besides reducing serum collagenases (MMP-3 and MMP-13) and collagen type II degradation biomarker (CTX-II) levels in these rats. The VA (containing various caffeoyl-quinic acids, flavanone-O-rutinoside, luteolin, apigenin derivative and vernonioside D) suppressed inflammation, pain, collagenases as well as cartilage degradation, and improved cartilage matrix synthesis to prevent OA.
Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p
The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.
A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.
Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon flavanones, 2,5-dihydroxy-7-methoxy flavanone 1 and 2,5-dihydroxy-6,7-dimethoxy flavanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy flavone 3 and 5-hydroxy-6,7-dimethoxy flavone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC(50) = 19.6 and 19.0 microM, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-deficient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer.
Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p
Following the current 'Globesity' trend, there is an increasing demand for alternative natural therapies for weight management. Numerous phytoconstituents reduce body weight through suppressing appetite and reducing food intake. Caraway (Carum carvi L.) is one of the medicinal plants that is traditionally used for weight loss. In this study, the appetite-suppressing effects of caraway aqueous extract (CAE) on 70 aerobically trained, overweight, and obese women were examined in a triple-blind, placebo-controlled, clinical study. Subjects were randomly allocated into placebo and experimental groups and consumed either 30 mL/day of CAE or placebo without changing their diet or physical activity over a period of 90 days. Calorie and macronutrient intake and anthropometric indices were measured before and after the intervention. In addition, appetite changes were assessed through a visual analog scale and an ad libitum pizza test. After the intervention, the results showed a significant reduction in appetite levels and carbohydrate intake of the experimental group compared with the placebo group. All of the anthropometric indices were reduced significantly in CAE compared with placebo group (p
Six aporphine and one phenanthrenoid alkaloids isolated from Aromadendron elegans Blume were investigated for their ability to inhibit arachidonic acid (AA), collagen and ADP induced platelet aggregation in human whole blood. The antiplatelet activity of the compounds was measured in vitro by the Chrono Log whole blood aggregometer using an electrical impedance method. Of the compounds tested, (-)-N-acetylnornuciferine, (-)-N-acetylanonaine and 1-(N-acetyl-N-methylamino)ethyl-3,4,6-trimethoxy-7-hydroxyphenanthrene showed strong inhibition on platelet aggregation caused by all three inducers. (-)-N-acetylanonaine was the most effective antiplatelet compound as it inhibited both arachidonic acid, collagen and ADP-induced platelet aggregation with IC(50) values of 66.1, 95.1 and 80.6 microm, respectively.
Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.
The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.
Phyllanthin, a lignan from Phyllanthus species, has been reported to possess potent immunosuppressive properties on immune cells and on adaptive and innate immune responses in animal models. Herein, we investigated the inhibitory effects of phyllanthin isolated from Phyllanthus amarus on nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and PI3K-Akt signal transducing pathways in LPS-activated U937 cells. The lipopolysaccharide-stimulated excess production of prostaglandin was significantly suppressed by phyllanthin via the mechanisms linked to the modulatory effects of cyclooxygenase 2 protein and gene expression. Phyllanthin also significantly inhibited the release and mRNA expression of proinflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha). Phyllanthin also significantly downregulated the phosphorylation of IκBα, NF-κB (p65), and IKKα/β and suppressed the activation of JNK, ERK, p38MAPK, and Akt in a concentration-dependent manner. Additionally, phyllanthin downregulated the expression of upstream signaling molecules including MyD88 and toll-like receptor 4 that are essential for the activation of NF-κB, MAPKs, and PI3K-Akt signal transducing pathways. Based on these observations, phyllanthin may exert their suppressive effects on inflammatory process by mediating the release of inflammatory signaling molecules via the NF-κB, MAPKs, and PI3K-Akt signal transducing pathways. Thus, phyllanthin holds a great promise as a potential anti-inflammatory agent to treat various inflammatory diseases.
Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L-NG-nitro arginine methyl ester (L-NAME), an analog of L-arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L-NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L-NAME-induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L-NAME-induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin-converting enzyme (ACE) and endothelin-1. Moreover, they exhibit anti-inflammatory effects, attenuating inflammation-mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L-NAME-induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.
Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.
Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.
Zingiber zerumbet rhizome has been used in traditional medicine mainly for the treatment of various immune-inflammatory related ailments and has been shown to exhibit a wide spectrum of biological effects especially antioxidant and anti-inflammatory activities. The present study was aimed to investigate the immunosuppressive effects of the standardized 80% ethanol extract of Z. zerumbet at 100, 200, and 400 mg/kg on the innate immune responses in male Wistar rats. The immune parameters determined were chemotaxis of neutrophils, Mac-1 expression, engulfment of Escherichia coli by neutrophils, reactive oxygen species production, and plasma lysozyme and ceruloplasmin levels. Zerumbone was qualitatively and quantitatively determined in the extract by using a validated reversed-phase HPLC, whereas liquid chromatography tandem-mass spectrometry (LC -MS/MS) was used to profile the secondary metabolites. Z. zerumbet significantly inhibited the migration of neutrophils, expressions of CD11b/CD18 integrin, phagocytic activity, and production of reactive oxygen species in a dose-dependent manner. The extract also dose-dependently inhibited the expressions of lysozyme and ceruloplasmin in the rat plasma. Z. zerumbet extract possessed strong inhibitory effects on the innate immune responses and has potential to be developed into an effective immunosuppressive agent.